The observation of an increased level of an amyloid precursor, serum amyloid A (SAA) protein, in many patients with neoplastic diseases led to this 5-year project proposal aiming at a comprehensive study of SAA in malignant diseases. The correlation of SAA levels with other parameters of neoplastic dissemination and the study of the biologic role, origin, synthesis and metabolic turnover of SAA are among its main objectives. Attempts will also be made to demonstrate SAA direct participation in the amyloid formation in vitro and in vivo, and to understand its role in various immune processes suggested by SAA elevation in all pathologic conditions accompanying the invasion by foreign antigens of mammalian organisms. Finally, the action of colchicine and vinca alkaloids on SAA synthesis and their possible beneficial effect in patients with amyloidosis will be investigated. With a radioimmunoassay, SAA levels will be monitored in 500 cases of cancer; from those with elevated levels, SAA will be extracted using gel filtration chromatography in formic acid and will be characterized by SDS acrylamide gel electrophoresis and peptide mapping. Its aggregation properties will be determined using radioactively iodinated SAA, which will also be injected into a few patients from whom it was initially extracted, for the study of SAA metabolic turnover. Using standard immunologic techniques, we shall also investigate the SAA role in vitro in: immunoglobulin production by B lymphocytes, lymphocyte membrance receptors, complement activity, lymphocyte blastic transformation, polynucleated granulocyte and monocyte function and its in vivo effects on mice prone to amyloid formation and on those resistant to it. It is hoped that the findings of this proposal will permit a better understanding of the pathogenesis of amyloidosis, especially that associated with malignant diseases, of the process of immune regulation in general, of its specific abnormalities in the course of neoplastic diseases, and will possibly help to find new methods for the prevention of amyloid formation and the correction of some of the abnormalities of the immune defense in patients with cancer.